The invention relates to sensors and sensor systems for detecting analytes in fluids.
There is considerable interest in developing sensors that act as analogs of the mammalian olfactory system (Lundstrom et al. (1991) Nature 352:47-50; Shurmer and Gardner (1992) Sens. Act. B 8:1-11; Shurmer and Gardner (1993) Sens. Act. B 15:32). In practice, most chemical sensors suffer from some interference by responding to chemical species that are structurally or chemically similar to the desired analyte. This interference is an inevitable consequence of the xe2x80x9clockxe2x80x9d being able to fit a number of imperfect xe2x80x9ckeysxe2x80x9d. Such interferences limit the utility of such sensors to very specific situations.
Arrays of broadly cross-reactive sensors have been exploited to produce response patterns that can be used to fingerprint, classify, and in some cases quantify analytes in fluids. Such arrays have been produced incorporating sensors including heated metal oxide thin film resistors (Gardner et al. (1991) Sens. Act. B4:117-121; Gardner et al. (1992) Sens. Act. B 6:71-75), polymer sorption layers on the surfaces of acoustic wave resonators (Grate and Abraham (1991) Sens. Act. B 3:85-111; Grate et al. (1993) Anal. Chem. 65:1868-1881), arrays of electrochemical sensors (Stetter et al. (1986) Anal. Chem. 58:860-866; Stetter et al. (1990) Sens. Act. B 1:43-47;Stetter et al. (1993) Anal. Chem. Acta 284:1-11), conductive polymers or composites that consist of regions of conductors and regions of insulating organic materials (Pearce et al. (1993) Analyst 118:371-377; Shurmer et al. (1991) Sens. Act. B 4:29-33; Doleman et al. (1998) Anal. Chem. 70:2560-2654; Lonergan et al. Chem. Mater. 1996, 8:2298). Arrays of metal oxide thin film resistors, typically based on tin oxide (SnO2) films that have been coated with various catalysts, yield distinct, diagnostic responses for several vapors (Corcoran et al. (1993) Sens. Act. B 15:32-37). Surface acoustic wave resonators are extremely sensitive to both mass and acoustic impedance changes of the coatings in array elements. Attempts have also been made to construct arrays of sensors with conducting organic polymer elements that have been grown electrochemically through use of nominally identical polymer films and coatings. Moreover, Pearce et al., (1993) Analyst 118:371-377, and Gardner et al., (1994) Sensors and Actuators B 18-19:240-243 describe polypyrrole based sensor arrays for monitoring beer flavor. Shurmer (1990) U.S. Pat. No. 4,907,441, describes general sensor arrays with particular electrical circuitry. U.S. Pat. No. 4,674,320 describes a single chemoresistive sensor having a semi-conductive material selected from the group consisting of phthalocyanine, halogenated phthalocyanine and sulfonated phthalocyanine, which was used to detect a gas contaminant. Other gas sensors have been described by Dogan et al., Synth. Met. 60, 27-30 (1993) and Kukla, et al. Films. Sens. Act. B., Chemical 37, 135-140 (1996).
Sensor arrays formed from a plurality of composites that consist of regions of a conductor and regions of an insulating organic material, usually an organic polymer as described in U.S. Pat. No. 5,571,401, have sensitivities that are primarily dictated by the swelling-induced sorption of a vapor into the composite material, and analytes that sorb to similar extents produce similar swellings and therefore produce similar detected signals (Doleman, et al., (1998) Proc. Natl. Acad. Sci. U.S.A, 95, 5442-5447).
In these systems, the different responses from an analyte exposure to the array of sensors is used to identify the analyte. Other properties of the devices are designed to insure that otherwise all sensors are nominally equivalent so that the fluid containing the analyte is delivered to all sensors equally effectivelyxe2x80x94for example, at the same temperaturexe2x80x94so that only the differences in sensors"" response properties are being measured.
Although these sensor systems have some usefulness, there remains a need in the art for highly-selective sensor arrays for detecting analytes and resolving the components of complex mixtures.
The present artificial olfactory systems (or electronic noses) use arrays of many receptors to recognize an odorant. In such a configuration, the burden of recognition is not on highly specific receptors, as in the traditional xe2x80x9clock-and-keyxe2x80x9d molecular recognition approach to chemical sensing, but lies instead on the distributed pattern processing of the olfactory bulb and the brain. The system takes advantage of the spatio-temporal response differences between nominally identical sensors that are located at different positions in a fluid flow pattern.
In general, in one aspect, the invention provides a method of detecting an analyte in a fluid. The method includes providing a sensor array including at least a first sensor and a second sensor in an arrangement having a defined fluid flow path; exposing the sensor array to a fluid including an analyte by introducing the fluid along the fluid flow path; measuring a response for the first sensor and the second sensor; and detecting the presence of the analyte in the fluid based on a spatio-temporal difference between the responses for the first and second sensors.
Particular implementations of the invention can include one or more of the following features. Detecting the presence of the analyte can include generating a spatio-temporal response profile indicative of the presence of the analyte based on the spatio-temporal difference between the responses for the first and second sensors. The spatio-temporal response profile can be derived from time information indicating the dependence of sensor response on time. The first sensor can be exposed to the fluid before the second sensor, such that the response of the second sensor is delayed with respect to the response of the first sensor. The first sensor can be exposed to the fluid before the second sensor, such that the response of the second sensor is changed in amplitude with respect to the response of the first sensor. The first sensor can include a sensing material; and the response of the first sensor can be greater than the response of the second sensor for an analyte having a high affinity for the sensing material. The first and second sensors can be selected and arranged to provide a first delay between the response of the first sensor and the response of the second sensor upon exposure of the sensor array to a fluid including a first analyte and a second delay between the response of the first sensor and the response of the second sensor upon exposure of the sensor array to a fluid including a second analyte. Measuring the response can include measuring the delay between the response of the first sensor and the response of the second sensor, and the spatio-temporal difference between the responses for the first and second sensors can be derived from the delay. The method can include characterizing the analyte based on the spatio-temporal difference between the responses. Exposing the sensor array to the fluid can include introducing the fluid at a varying flow rate. Generating the spatio-temporal response profile can include generating flow information indicating the dependence of sensor response on flow rate. The sensor array can include a plurality of cross-reactive sensors. The sensor array can include a plurality of sensors selected from the group including surface acoustic wave sensors, quartz crystal resonators, metal oxide sensors, dye-coated fiber optic sensors, dye-impregnated bead arrays, micromachined cantilever arrays, composites having regions of conducting material and regions of insulating organic material, composites having regions of conducting material and regions of conducting or semiconducting organic material, chemically-sensitive resistor or capacitor films, metal-oxide-semiconductor field effect transistors, and bulk organic conducting polymeric sensors. The first and second sensors can include composites having regions of a conducting material and regions of an insulating organic material. The first and second sensors can include composites having regions of a conducting material and regions of a conducting organic material. The method can include generating a digital representation of the analyte based at least in part on the responses of the first and second sensors. The method can include communicating the digital representation of the analyte to a remote location for analysis.
In general, in another aspect, the invention provides a system for detecting an analyte in a fluid. The system includes a sensor array including at least a first sensor and a second sensor in an arrangement having a defined fluid flow path; a measuring apparatus coupled to the sensor array, the measuring apparatus being configured to detect a response from the first sensor and the second sensor upon exposure of the sensor array to a fluid; and a computer configured to generate data indicating the presence of the analyte in the fluid based on a spatio-temporal difference between the responses for the first and second sensors.
Particular implementations of the invention can include one or more of the following features. The data indicating the presence of the analyte in the fluid can include a spatio-temporal response profile derived from the spatio-temporal difference between the responses for the first and second sensors. The spatio-temporal response profile is derived from time information indicating the dependence of sensor response on time. The first sensor can occupy a first position in the arrangement and the second sensor a second position in the arrangement, such that the response of the second sensor is delayed in time with respect to the response of the first sensor upon exposure of the sensor array to the fluid. The first sensor can occupy a first position in the arrangement and the second sensor a second position in the arrangement, such that the response of the second sensor is changed in amplitude with respect to the response of the first sensor upon exposure of the sensor array to the fluid. The first sensor can include a sensing material, and the response of the first sensor can be greater than the response of the second sensor for an analyte having a high affinity for the sensing material. The first and second sensors can be selected and arranged to provide a first delay between the response of the first sensor and the response of the second sensor upon exposure of the sensor array to a fluid including a first analyte and a second delay between the response of the first sensor and the response of the second sensor upon exposure of the sensor array to a fluid including a second analyte. The measuring apparatus can be configured to measure the delay between the response of the first sensor and the response of the second sensor; and the spatio-temporal difference between the responses for the first and second sensors can be derived from the delay. The computer can be configured to characterize the analyte based on the spatio-temporal difference between the responses. The system can include a flow controller to introduce the fluid to the sensor array at a varying flow rate. The computer can be configured to generate flow information indicating the dependence of sensor response on flow rate. The sensor array can include a plurality of cross-reactive sensors. The sensor array can include a plurality of sensors selected from the group including surface acoustic wave sensors, quartz crystal resonators, metal oxide sensors, dye-coated fiber optic sensors, dye-impregnated bead arrays, micromachined cantilever arrays, composites having regions of conducting material and regions of insulating organic material, composites having regions of conducting material and regions of conducting or semiconducting organic material, chemically-sensitive resistor or capacitor films, metal-oxide-semiconductor field effect transistors, and bulk organic conducting polymeric sensors. The first and second sensors can include composites having regions of a conducting material and regions of an insulating organic material. The first and second sensors can include composites having regions of a conducting material and regions of a conducting organic material. The computer can be configured to generate a digital representation of the analyte based at least in part on the responses of the first and second sensors. The system can include a communications port coupled to the computer for communicating the digital representation of the analyte to a remote location for analysis.
In general, in still another aspect, the invention provides a system for detecting an analyte in a fluid. The system includes a sensor array including a first sensor and a second sensor, a fluid inlet proximate to the sensor array, and a measuring apparatus connected to the sensor array. The fluid inlet defines a fluid flow pattern for the introduction of a fluid onto the sensor array, such that the first and second sensors are located at different locations in the sensor array relative to the fluid flow pattern. The measuring apparatus is configured to detect a response from the first sensor and the second sensor upon exposure of the sensor array to a fluid. The responses define a spatio-temporal difference between the responses for the first and second sensors based on the locations of the sensors relative to the fluid flow pattern.
Particular implementations of the invention can include one or more of the following features. The spatio-temporal difference can be derived from time information indicating the dependence of sensor response on time. The first sensor can occupy a first position relative to the fluid flow pattern and the second sensor a second position relative to the fluid flow pattern, such that the response of the second sensor is delayed with respect to the response of the first sensor upon exposure of the sensor array to the fluid. The first sensor can occupy a first position relative to the fluid flow pattern and the second sensor a second position relative to the fluid flow pattern, such that the response of the second sensor is changed in amplitude with respect to the response of the first sensor upon exposure of the sensor array to the fluid. The first sensor can include a sensing material and the response of the first sensor can be greater than the response of the second sensor for an analyte having a high affinity for the sensing material. The first and second sensors can be selected and arranged to provide a first delay between the response of the first sensor and the response of the second sensor upon exposure of the sensor array to a fluid including a first analyte and a second delay between the response of the first sensor and the response of the second sensor upon exposure of the sensor array to a fluid including a second analyte. The measuring apparatus can be configured to measure the delay between the response of the first sensor and the response of the second sensor, and the spatio-temporal difference between the responses for the first and second sensors can be derived from the delay. The system can include a computer configured to characterize the analyte based on the spatio-temporal difference between the responses. The system can include a flow controller to introduce the fluid to the sensor array at a varying flow rate. The measuring apparatus can be configured to measure flow information indicating the dependence of sensor response on flow rate. The sensor array can include a plurality of cross-reactive sensors. The system sensor array can include a plurality of sensors selected from the group including surface acoustic wave sensors, quartz crystal resonators, metal oxide sensors, dye-coated fiber optic sensors, dye-impregnated bead arrays, micromachined cantilever arrays, composites having regions of conducting material and regions of insulating organic material, composites having regions of conducting material and regions of conducting or semiconducting organic material, chemically-sensitive resistor or capacitor films, metal-oxide-semiconductor field effect transistors, and bulk organic conducting polymeric sensors. The first and second sensors can include composites having regions of a conducting material and regions of an insulating organic material. The first and second sensors can include composites having regions of a conducting material and regions of a conducting organic material. The computer can be configured to generate a digital representation of the analyte based at least in part on the responses of the first and second sensors.
In general, in still another aspect, the invention provides a system for detecting an analyte in a fluid. The system includes a sensor array including a first sensor and a second sensor; a fluid flow exposing the first and second sensors to a fluid, such that the first and second sensors occupy different locations in the sensor array relative to the fluid flow; and a measuring apparatus connected to the sensor array. The measuring apparatus is configured to detect a response from the first and second sensors upon exposure of the sensor array to the fluid flow. The responses define a spatio-temporal difference based on the locations of the sensors in the sensor array relative to the fluid flow.
Particular implementations of the invention can include one or more of the following features. The spatio-temporal difference can be derived from time information indicating the dependence of sensor response on time. The first sensor can occupy a first position relative to the fluid flow and the second sensor a second position relative to the fluid flow, such that the response of the second sensor is delayed with respect to the response of the first sensor upon exposure of the sensor array to the fluid. The first sensor can occupy a first position relative to the fluid flow and the second sensor occupies a second position relative to the fluid flow, such that the response of the second sensor is changed in amplitude with respect to the response of the first sensor upon exposure of the sensor array to the fluid. The first sensor can include a sensing material, and the response of the first sensor can be greater than the response of the second sensor for an analyte having a high affinity for the sensing material. The first and second sensors can be selected and arranged to provide a first delay between the response of the first sensor and the response of the second sensor upon exposure of the sensor array to a fluid including a first analyte and a second delay between the response of the first sensor and the response of the second sensor upon exposure of the sensor array to a fluid including a second analyte. The measuring apparatus can be configured to measure the delay between the response of the first sensor and the response of the second sensor, and the spatio-temporal difference between the responses for the first and second sensors can be derived from the delay. The system can include a computer configured to characterize the analyte based on the spatio-temporal difference between the responses. The system can include a flow controller to vary the rate of the fluid flow. The measuring apparatus can be configured to measure flow information indicating the dependence of sensor response on flow rate. The sensor array can include a plurality of cross-reactive sensors. The sensor array can include a plurality of sensors selected from the group including surface acoustic wave sensors, quartz crystal resonators, metal oxide sensors, dye-coated fiber optic sensors, dye-impregnated bead arrays, micromachined cantilever arrays, composites having regions of conducting material and regions of insulating organic material, composites having regions of conducting material and regions of conducting or semiconducting organic material, chemically-sensitive resistor or capacitor films, metal-oxide-semiconductor field effect transistors, and bulk organic conducting polymeric sensors. The first and second sensors can include composites having regions of a conducting material and regions of an insulating organic material. The first and second sensors can include composites having regions of a conducting material and regions of a conducting organic material. The computer can be configured to generate a digital representation of the analyte based at least in part on the responses of the first and second sensors.
In general, in still another aspect, the invention provides a sensor array for detecting an analyte in a fluid. The sensor array includes a substrate; a first sensor coupled to the substrate at a first location; and a second sensor coupled to the substrate at a second location, such that the first and second sensors occupy different locations in the sensor array relative to a fluid flow path.
Particular implementations of the invention can include one or more of the following features. The first sensor can occupy a first position relative to the fluid flow path and the second sensor a second position relative to the fluid flow path, the first sensor being configured to provide a first response upon exposure of the sensor array to a fluid and the second sensor being configured to provide a second response upon exposure of the sensor array to the fluid, such that the second response is delayed with respect to the first response upon exposure of the sensor array to the fluid. The first sensor can provide a first time-dependent response upon exposure of the sensor array to a fluid, and the second sensor can provide a second time-dependent response upon exposure of the sensor array to the fluid. The first sensor can occupy a first position relative to the fluid flow path and the second sensor a second position relative to the fluid flow path, such that the second time-dependent response is changed in amplitude with respect to the first time-dependent response upon exposure of the sensor array to the fluid. The first sensor can include a sensing material, and the response of the first sensor can be greater than the response of the second sensor for an analyte having a high affinity for the sensing material. The first and second sensors can be selected and arranged to provide a first delay between a response of the first sensor and a response of the second sensor upon exposure of the sensor array to a fluid including a first analyte and a second delay between a response of the first sensor and a response of the second sensor upon exposure of the sensor array to a fluid including a second analyte. The sensor array can include a plurality of cross-reactive sensors. The sensor array can include a plurality of sensors selected from the group including surface acoustic wave sensors, quartz crystal resonators, metal oxide sensors, dye-coated fiber optic sensors, dye-impregnated bead arrays, micromachined cantilever arrays, composites having regions of conducting material and regions of insulating organic material, composites having regions of conducting material and regions of conducting or semiconducting organic material, chemically-sensitive resistor or capacitor films, metal-oxide-semiconductor field effect transistors, and bulk organic conducting polymeric sensors. The first and second sensors can include composites having regions of a conducting material and regions of an insulating organic material. The first and second sensors can include composites having regions of a conducting material and regions of a conducting organic material.
Advantages that can be seen in implementations of the invention include one or more of the following. Taking advantage of a spatio-temporal property of a sensor array can impart very useful information on analyte identification and detection relative to arrays where no spatio-temporal information is available because all sensors are nominally in identical positions with respect to the fluid flow characteristics and are exposed to the analyte at nominally identical times during the fluid sampling experiment. Electronics can be implemented to record the time delay between sensor responses and to use this information to characterize the analyte of interest in the fluid. This mode can also be advantageous because it can allow automatic nulling of any sensor drift, environmental variations (such as temperature, humidity, etc.) and the like. Also, a complex odor mixture can be better resolved into its components based on the spatiotemporal characteristics of the array response relative only to the differences in fingerprints on the various sensors types in the array. Additionally, these techniques can be used in conjunction with differential types of measurements to selectively detect only certain classes or types of analytes, because the detection can be gated to only focus on signals that exhibit a desired correlation time between their responses on the sensors that are in different exposure times relative to the sensor response on the first sensor that detects an analyte.